| Objective: This study is to provide a reference for further development of the clinical application of the tanshinone ⅡA(TA). Herein, the high drug loading and encapsulation efficiency of TA microspheres were prepared, and the pharmaceutical properties and the in vitro drug release behavior of microspheres were investigated assessed. To prevent drug photolysis reaction, improve its stability, and can achieve a suitable release effect, reduce the number of clinical medicine, and even reduce the dose, to improve patient compliance. Methods: Established UV-VIS spectrophotometry determination for the content and in vitro cumulative release of TA microspheres. The optimum polymer material and preparation process were clarified by the comprehensive weighted score which was evaluated with the the drug loading, encapsulation efficiency, and yield. PLLA, PDLLA, PDLLA-PEG-PDLLA, m PEG-PDLLA as carrier material to TA microspheres.The drug loading and encapsulation efficiency of the microspheres were investigated and the conditions were optimized of TA microspheres. Microspheres resulting from the optimized method were then characterized by scanning electron microscopy, fourier transform infrared(FT-IR) spectroscopy and X-ray diffraction(XRD), and the in vitro drug release behavior was assessed. Results: The precision, reproducibility, stability, and recovery compliance of the methods were good, to which determination of drug content and in vitro cumulative release. The surface of PLLA tanshinone ⅡA microspheres was round and has porous structure, average particle size was(96.95 ± 1.70) μm, the drug loading was(30.43 ± 0.04) %, the entrapment efficiency was(82.72 ± 1.51) %, and the yield was(94.10 ± 1.60) %. PDLLA prepared microspheres were spherical and exhibited a regular, uniform distribution, no adhesion was observed, and the surfaces of the microspheres exhibited crack shape. The microspheres with an average particle size of(98.55 ± 1.33) μm, the drug loading was(30.46 ± 0.03) %, the encapsulation rate was(73.48 ± 1.67) %, and the yield was(91.49 ± 2.11) %. The PDLLA-PEG-PDLLA microspheres were regularly shaped and spherical, while the surface had a flakily structure. The mean particle size was(103.5 ± 1.51) μm, the drug loading was(27.84 ± 0.36) %, the encapsulation efficiency was(77.33 ± 2.82) % and the yield was(92.59 ± 2.22) %. The m PEG-PDLLA microspheres were regularly shaped and spherical, while the surface had a cross-flakily structure. The mean particle size was(136.4 ± 1.54) μm, the drug loading was(25.58 ± 0.04) %, the encapsulation efficiency was(72.76 ± 0.54) % and the yield was(88.28 ± 0.68) %. Analyzed the interaction of drugs and materials and crystal phase changes by FT-IR, XRD, the results showed that the drug has been successfully incorporated into the microspheres and that the peak was not a result of physical mixing, and chemical reactions did not take place during preparation and that it was a physical process of the drug being wrapped by the polymer microspheres. It was consequently concluded that the drug remained in a crystalline form in the microspheres. PLLA-TA microspheres, PDLLA-TA microspheres, PDLLA-PEG-PDLLA-TA microspheres, m PEG-PDLLA-TA microspheres with PBS as medium separately in vitro release reached 6.44%, 20.49%, 23.59% and 29.55% after 792 h, while the free TA was just 2.99% through the dialysis membrane. But the n-butanol as the release medium, 80% cumulative release of microspheres were 72 h, and cumulative release to complete were 120 h, 168 h, 240 h and 336 h. Under the same conditions, free TA release fully was within 24 h. Conclusion: Microspheres of TA were successfully prepared by emulsion solvent evaporation method. TA microspheres had significantly high drug loading and encapsulation efficiency, and had a good sustained release function. And the optimal process was simple and reasonable, which is base for further research. |
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